[Current concepts concerning the oxygen affinity for hemoglobin].
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Biomedical subjects
Publications and source records attributed to S Carlone.
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When an alternating current of high frequency is applied to the thorax, the first derivative of the impedance (dZ/dt) is affected by the cardiac cycle, resulting in a characteristic wave form. The maximum negative of this wave occurring during systole together with the length of ejection time (VET), the blood resistivity, the basal impedance (ZO) and the distance between the inner detecting electrodes (L) makes it possible to calculate stroke volume (SV) and related parameters, as cardiac output (CO) and cardiac index (Cl) by a formula developed by Kubicek. Thoracic electrical impedance has been proposed as a non invasive technique to evaluate cardiac emodinamics. In the present study we have evaluated thoracic electrical impedance by comparing it with thermodilution, simultaneously performed in 21 catheterized patients. Reproducibility was assessed by comparing Cl measured several times in the same patient during ten minutes of rest in the supine position: coefficient of variation, expressed as CV = SD/m X 100 was 8,5 +/- 4,2% and 9,4 +/- 3,2% (p = NS) for thermodilution and thoracic electrical impedance respectively. Cl values obtained by both methods correlated well, with little scatter either baseline (r = 0,784, n = 40, p less than 0,001), either after an handgrip manoeuvre (r = 0,629, n = 15, p less than 0,05). This degree of correlation is similar to that observed comparing invasive techniques (Fick, thermodilution, dye dilution) either among them, or with noninvasive methods (echocardiography, gated equilibrium blood pool scintigraphy and ultrasonic Doppler).(ABSTRACT TRUNCATED AT 250 WORDS)
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Combinations of penicillin G sodium or ampicillin plus streptomycin sulfate do not produce synergism against all strains of enterococci. This lack of synergism was considered the cause of the failure in the treatment of enterococcal endocarditis. The effect of various combinations of antibiotics on 15 enterococcus strains, which had been isolated from patients with enterococcal endocarditis, was examined. The antibiotics included those that interfere with cell-wall synthesis and those that act on cell metabolism. The in vitro results have shown that while penicillin- or ampicillin-streptomycin combination was not synergistic in eight of 15 strains, penicillin- or ampicillin-gentamicin sulfate combination was synergistic in 100% of the cases. We report seven cases of enterococcal endocarditis that were successfully treated with penicillin- or ampicillin-gentamicin combination, thus confirming the effectiveness of this therapeutic regimen.
The pathogenesis of Kaposi's sarcoma (KS) is still unclear, and several factors appear to be involved in the onset of the Kaposi's lesion. Epidemiological studies suggest that a common infective agent may contribute to KS. Sequences which appear to represent a new gammaherpesvirus, currently termed KSHV/HHV8, have recently been identified in KS. To further examine the relationship between this virus and KS, we obtained biopsy samples of KS lesions; these samples, the spindle cells cultured from these lesions and the PBMC of the same patients were tested for the presence of KSHV sequences by PCR. In addition, we tested several "late passage" KS spindle cell lines as well as control samples. The biopsy samples were from lesions of the following forms of KS: one sporadic KS, two epidemic KS and three iatrogenic KS, one of which was in the process of regressing after reduction of immunosuppressive therapy, and two that were at different stages (patch and nodular) from a single patient. The sporadic KS specimen was positive, as were the PBMCs from this patient, and cells grown from this biopsy appeared to contain KSHV viral sequences up to the fifth passage. Both epidemic KS biopsies were positive, but in these cases KSHV sequences were not detected in the cultured cells. The biopsy from the regressing iatrogenic KS lesion was negative, as were the cells cultured from this lesion. However, the PBMCs of this patient were weakly positive for KSHV at the time of biopsy, and PBMCs collected from this patient one month later were completely negative. The samples of both the patch and the nodular KS lesions obtained from another immunosuppressed patient showed amplifiable sequences of KSHV, but both the PBMCs of this patient and primary KS cell cultures from these biopsies were negative. Of the late-passage KS lines tested, only one, IST AIDS KS 12, was positive for KSHV. This line is derived from an early angiomatous-macula lesion. Taken together, these data suggest that an active KSHV infection is associated with KS and that elimination of KSHV from the lesion precedes regression of the lesion, strongly correlating KSHV with KS. In addition, early KS lesions may have a higher KSHV burden, or contain cells more susceptible to KSHV infection, further linking KSHV to KS.
We have established and characterized two new Kaposi's sarcoma (KS) cell lines derived from skin biopsies: AIDS-KSISTIV (from an AIDS-associated KS) and KSISTVIII (from a sporadic KS). AIDS-KSISTIV and KSISTVIII are composed mostly of spindle-shaped cells. They show similar patterns of immunohistochemical staining and are positive for smooth muscle (smooth muscle alpha-actin) and fibroblastoid (TE7) markers. Neither of these lines express the endothelial marker von Willebrand factor VIII. These immunohistochemical patterns are similar to numerous other KS lines that we and others have established. When seeded on a reconstituted basement membrane ("Matrigel"), AIDS-KSISTIV and KSISTVIII cells form branching colonies and invade into the Matrigel, as do other KS cultures that we have previously examined. This behaviour on Matrigel is similar to that of malignant sarcoma cells of different origin. The expression of vimentin and the morphology of the invasive colonies on Matrigel suggest that KS-derived cells are poorly differentiated mesenchymal cells. KS lesions are characterized by a conspicuous neovascularization, which appears to be derived from host cell recruitment. We tested the capability of the KS-cell supernatants to induce an angiogenic response in vitro. The new lines are able to stimulate human endothelial cell chemotaxis and invasion through Matrigel-coated filters. No differences in angiogenic potential in vitro were observed between the AIDS and the non-AIDS case, as we previously noted for other established cultures. Our new lines have the properties of true KS cells and confirm that KS spindle cells from HIV-positive or -negative patients have identical phenotypic and behavioural characteristics in vitro.
The behavior of the oxyhemoglobin curve was studied in ten patients with respiratory alkalosis (arterial [H+] less than 37 nM, pCO2 less than 32 mmHg and HCO-3 less than 22.0 mEq/L) and ten patients with metabolic alkalosis ([H+] less than 34 nM, pCO2 greater than 37 mmHg and HCO-3 greater than 28.0 mEq/L) to determine whether different alkalotic states similarly affect the red blood cell [H+] and 2,3-diphosphoglycerate interaction and thus the oxygen affinity of hemoglobin. The findings were statistically indistinguishable in respiratory alkalosis and metabolic alkalosis: a) low plasma [H+], normal red blood cell [H+], and high transmembrane [H+] gradient; b) elevated red blood cell 2,3-diphosphoglycerate inversely proportional to low arterial plasma [H+]; c) decrease in oxygen affinity of hemoglobin when normalized for plasma [H+], but less decreased when normalized for red blood cell [H+]. Other factors capable of affecting the oxygen affinity of hemoglobin were: mean corpuscular hemoglobin concentration; red blood cell adenosine triphosphate; carboxyhemoglobin; and methemoglobin were not significantly different between groups. These results: 1) agree with data previously reported from this laboratory on patients with portal-systemic encephalopathy; 2) underscore the importance of RBC [H+] in defining the oxygen affinity of hemoglobin; 3) suggest the decrease in oxygen affinity of hemoglobin is mediated through the 2,3-diphosphoglycerate elevation; and 4) indicate the high transmembrane [H+] gradient is principally due to the cellular accumulation of [H+] (2,3-diphosphoglycerate ionization).
The role of oncogenes in the acquisition of invasive and metastatic capabilities is controversial. Interactions with basement membranes are critical in the process of tumor invasion and metastasis. We compared the ability of 3T3 cells transformed by oncogenes involved in various stages of signal transduction to invade a reconstituted basement membrane in vitro and to grow in a three dimensional basement membrane gel (matrigel). Cell lines transformed by various oncogenes and oncoviruses: v-sis (a growth factor), v-erb-B (a truncated EGF receptor), Moloney sarcoma virus (v-mos: a protein kinase homologue), mutated c-ras oncogenes (G protein homologues), FBJ virus (v-fos: a nuclear protein) were investigated. All transformed cell lines were able to invade in the chemoinvasion assay, where a layer of matrigel is coated onto chemotaxis filters. FBJ/3T3 were the least invasive and SSV/3T3 the most invasive. Control 3T3 cells could not cross the matrigel barrier. All transformed cells grew on matrigel forming invasive, branching colonies, whereas control 3T3 were unable to grow in matrigel. Cells transfected with the v-erb-B gene grew as multilayers inside matrigel. Invasiveness and growth on matrigel were accompanied by a high chemotactic response to laminin (LN) in all transformed lines. These results suggest that invasion and growth on matrigel, together with migration to LN, are induced by a large spectrum of oncogenes. When 3T3 cells were transfected with v-sis oncogene under the transcriptional control of the metallothionein (MMT) promoter and exposed to Zn++, their in vitro invasiveness was specifically increased by around 3 fold. These findings provide further evidence supporting a direct role of the v-sis oncogene in the invasive phenotype.
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